Discover. Oncology最新文献

{"title":"Comprehensive pan-cancer evaluation of NUP85 prognosis, immune infiltration response, and validation in prostate cancer.","authors":"Zhijun Chen, Han Guan, Long Chen, Xinwei Yuan, Wenyan Sun, Ming Chen","doi":"10.1007/s12672-025-03735-1","DOIUrl":"https://doi.org/10.1007/s12672-025-03735-1","url":null,"abstract":"<p><strong>Background: </strong>Although NUP85 is a member of the nuclear pore complex (NPC) and is associated with chromosome variation and tumor regulation, its specific role in cancer development remains unclear and requires further research.</p><p><strong>Methods: </strong>This study analyzes the mRNA and protein levels of NUP85 in normal and tumor tissues using the TCGA, GTEx, and HPA databases. We investigated the relationship between NUP85 and survival rates, as well as clinical features, in various tumors by analyzing the TCGA database. The expression pattern of NUP85 in cancer cells is analyzed using single-cell sequencing data from the TISCH database. Two types of prostate cancer cell lines are utilized to investigate the impact of NUP85 on cell proliferation, migration, invasion, and apoptosis, as well as its regulatory mechanism. These analyses aim to uncover the role of NUP85 in cancer, particularly in prostate cancer.</p><p><strong>Results: </strong>NUP85 is observed to exhibit elevated expression levels across multiple malignancies, with its heightened expression showing consistent associations with poorer clinical prognoses. Bioinformatic analyses further reveal that NUP85 expression patterns demonstrate significant correlations with the activity of cancer-related pathways and immunological interactions involving macrophages and T cell populations. Notably, experimental studies using prostate cancer models have documented reduced cellular proliferation following NUP85 knockout, suggesting a potential functional connection warranting further mechanistic investigation.</p><p><strong>Conclusions: </strong>The results indicate that elevated NUP85 expression shows strong correlations with cancer initiation and progression. These findings support its potential utility as a candidate biomarker for disease monitoring across various malignancies, though mechanistic validation remains necessary to establish clinical applicability.</p>","PeriodicalId":11148,"journal":{"name":"Discover. Oncology","volume":"16 1","pages":"1953"},"PeriodicalIF":2.9,"publicationDate":"2025-10-22","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145344162","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Kaempferols from Echinacea purpurea demonstrate anti-cancer potential by targeting anexelekto in breast cancer therapy using chemoinformatics approach.","authors":"Saviour God'swealth Usin, Daniel Ogbonnaya Nwankwo, Anas Haruna Ruggah, Adebesin Ayomide Oluwadarasimi, Md Ahad Ali, Timothy Oluwatimileyin Ayeni, Abass Abdulateef Ohilebo, Abdulsamad Omotayo Aiyelabegan, Opeyemi Christianah De Campos, Kayode Raheem Yomi, Siham Lakrikh, Awotunde Oluwasegun Samson, Cornelius Ayodeji Aboderin, Bodun Damilola Samuel, Abdulwasiu Ibrahim, Toheeb Adewale Balogun","doi":"10.1007/s12672-025-03541-9","DOIUrl":"https://doi.org/10.1007/s12672-025-03541-9","url":null,"abstract":"&lt;p&gt;&lt;strong&gt;Background: &lt;/strong&gt;Breast cancer is one of the most common cancer types among women, especially in developing and underdeveloped nations like Nigeria. Anexelekto (AXL) is one of the well-known proteins that is implicated in various cancer types, including breast cancer, and it remains one of the focuses of targeted therapy. However, several drugs have been identified as inhibitors of this oncogenic protein, but they often come with toxic concerns in addition to their unaffordability to people of low- or middle-income countries. Thus, there is a crucial need to identify pocket-friendly inhibitors with negligible side effects targeting AXL. Therefore, bioactive compounds from plants such as Echinacea purpurea may be a promising agent in this regard.&lt;/p&gt;&lt;p&gt;&lt;strong&gt;Objective: &lt;/strong&gt;The study sought to investigate the potential of bioactive compounds derived from Echinacea purpurea to inhibit the AXL protein implicated in breast cancer.&lt;/p&gt;&lt;p&gt;&lt;strong&gt;Methods: &lt;/strong&gt;Structural bioinformatics via molecular docking and density functional theory (DFT) analysis was utilised for the identification of novel AXL inhibitors from Echinacea purpurea bioactive compounds. The compounds were further subjected to pharmacokinetic and drug-likeness analysis. Results obtained from the compounds were compared against those of Foretinib, a known AXL inhibitor. Additionally, their complexes with AXL were subjected to a 100 ns molecular dynamics (MD) simulation analysis utilising the Desmond v2020-4 software in Schrödinger (Academic version) in a Linux environment.&lt;/p&gt;&lt;p&gt;&lt;strong&gt;Results: &lt;/strong&gt;Among all favourable binding scores, Kaempferol-7-o-Neohesperidoside, Kaempferol 3-gentiobioside-7-rhamnoside, and Kaempferol 3-o-beta-d-glucopyranosyl-7-o-alpha-L-rhamnopyranoside showed the highest binding score of -9.2, -8.9, and - 8.6 Kcal/mol, respectively, compared to Foretinib (-8.1 Kcal/mol). Stigmasterol and β-sitosterol also showed a higher binding affinity and binding score of -8.4 and - 8.3 Kcal/mol, respectively, against the AXL compared to the standard drug. DFT analysis revealed that Kaempferol 3-o-beta-d-glucopyranosyl-7-o-alpha-L-rhamnopyranoside has the highest LUMO-HOMO gap of -4.354 eV, suggesting greater potential for electron donation and high drug-enzyme reactivity. Also, the pharmacokinetic profiling of the selected compounds is favourable. Findings from MD simulation showed that the protein-ligand complexes formed by these compounds maintained structural stability, compactness, and low atomic fluctuations throughout a 100-ns simulation period.&lt;/p&gt;&lt;p&gt;&lt;strong&gt;Conclusion: &lt;/strong&gt;In silico studies show that E. purpurea-derived compounds, especially Kaempferol 3-o-beta-d-glucopyranosyl-7-o-alpha-L-rhamnopyranoside, have better inhibitory potential against AXL and better pharmacokinetic profiles when compared with Foretinib. These compounds are thus proposed as novel AXL inhibitors for the treatment of breast cancer. Further, in vivo studies","PeriodicalId":11148,"journal":{"name":"Discover. Oncology","volume":"16 1","pages":"1954"},"PeriodicalIF":2.9,"publicationDate":"2025-10-22","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145343878","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Prognostic significance of GPR132 in papillary thyroid carcinoma: insights from integrated machine learning and its role in regulating TPC-1 cell growth.","authors":"Jinghua Gao, Zihan Cai, Shoupeng Ding, Lanxin Ma, Jian Han, Yi-Yi Luo, Xueli Yang, Liqin Zhou, Wen Mei, Xiangfang Li, Lin Meng, Heng Luo","doi":"10.1007/s12672-025-03833-0","DOIUrl":"https://doi.org/10.1007/s12672-025-03833-0","url":null,"abstract":"<p><strong>Object: </strong>This study utilizes machine learning and bioinformatics methods to analyze data identifying GPR132 as a reliable potential prognostic gene for papillary thyroid carcinoma (PTC).The experiments elucidated potential role of GPR132 in inhibiting tumor growth in PTC by regulating the cell cycle and apoptotic mechanisms. This research provides significant insights for future personalized therapeutic strategies aimed at targeting PTC.</p><p><strong>Methods: </strong>The study analyzed the GSE191288 RNA-seq dataset, which included six thyroid cancer tumor samples and one adjacent normal tissue sample, to identify genes associated with tumor-associated macrophages (TAMs). After conducting a thorough enrichment analysis, we used the CellChat tool to investigate the signaling pathways.Pseudotemporal analysis elucidated the differentiation status of TAMs, and weighted gene co-expression network analysis(WGCNA) identified M1-like TAM-related genes within the M1 macrophage module. Integration with the GEO database revealed that GPR132 is a key prognostic gene. The effects of GPR132 overexpression on the proliferation, migration, apoptosis, and cell cycle progression of thyroid papillary carcinoma (TPC-1) cells were evaluated through cell-based experiments.</p><p><strong>Results: </strong>Single-cell sequencing revealed 20 distinct cell clusters, categorized as epithelial, stromal, or immune cells, with a focus on TAMs.Enrichment analysis associated TAM-expressed genes with immune response regulation. Pseudotime analysis identified TAMs differentiation states, while WGCNA linked a low abundance of M1 macrophages to favorable PTC prognosis. Integration with the GEO database confirmed GPR132 as a key prognostic gene. Cellular experiments showed that GPR132 overexpression markedly inhibited TPC-1 cell proliferation and migration, likely through G1 phase cell cycle arrest and enhanced apoptosis. Flow cytometry confirmed elevated early and total apoptosis rates in GPR132-overexpressing cells.</p><p><strong>Conclusion: </strong>GPR132 was identified as a critical prognostic gene for PTC, with evidence suggesting its role in tumor suppression via cell cycle modulation and apoptosis induction.</p>","PeriodicalId":11148,"journal":{"name":"Discover. Oncology","volume":"16 1","pages":"1956"},"PeriodicalIF":2.9,"publicationDate":"2025-10-22","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145343883","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Current strategies and novel immunotherapeutic approaches for overcoming immune resistance in glioblastoma.","authors":"Mehrdad Nourizadeh, Saeid Mohammadzadeh Mounesyar, Mahdi Salimi Movahhed, Kasra Alipour, Rozhan Zekavatbakhsh, Mobina Hoseinzadeh, Shaghayegh Davari, Mehdi Amirhooshangi, Hadi Amirhoushangi, Sina Hamzehzadeh","doi":"10.1007/s12672-025-03807-2","DOIUrl":"https://doi.org/10.1007/s12672-025-03807-2","url":null,"abstract":"","PeriodicalId":11148,"journal":{"name":"Discover. Oncology","volume":"16 1","pages":"1952"},"PeriodicalIF":2.9,"publicationDate":"2025-10-22","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145344174","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Peripheral SNCA⁺ cells as a poor prognostic factor for nivolumab therapy in advanced gastric cancer.","authors":"Chie Kudo-Saito, Hiroshi Imazeki, Kengo Nagashima, Hirokazu Shoji, Kai Tsugaru, Naoki Takahashi, Takeshi Kawakami, Yusuke Amanuma, Takeru Wakatsuki, Naohiro Okano, Yukiya Narita, Yoshiyuki Yamamoto, Rika Kizawa, Kei Muro, Narikazu Boku","doi":"10.1007/s12672-025-03817-0","DOIUrl":"https://doi.org/10.1007/s12672-025-03817-0","url":null,"abstract":"<p><strong>Background: </strong>We previously demonstrated that immune cells expressing α-synuclein (SNCA) are dramatically increased in peripheral blood of patients with gastric cancer (GC), but rarely in healthy donors, and that blocking SNCA is significantly effective even in anti-PD1-resistant mouse tumor models with increased SNCA⁺ cells. This suggests that the increased SNCA⁺ cells are involved in resistance to anti-PD1 therapy. However, the relationship between SNCA⁺ cell levels and anti-PD1/PDL1 therapeutic efficacy in GC remains to be determined in clinical settings.</p><p><strong>Methods: </strong>In the WJOG10417GTR study, peripheral blood cells collected from advanced GC patients before and one month after nivolumab monotherapy were analyzed for several SNCA⁺ cell populations by flow cytometry, and the relationship between the levels and patient prognosis was statistically analyzed.</p><p><strong>Results: </strong>High levels of SNCA⁺ cells, particularly the myeloid subset, before and after treatment were significantly associated with shorter progression-free survival and overall survival. Patients with low SNCA⁺ cell levels survived for a long time without disease progression, indicating durable responders.</p><p><strong>Conclusion: </strong>These suggest that SNCA⁺ cells are significant poor prognostic factors in nivolumab therapy for advanced GC. Targeting SNCA may be a promising strategy to improve clinical outcomes in anti-PD1/PDL1 therapy for GC.</p>","PeriodicalId":11148,"journal":{"name":"Discover. Oncology","volume":"16 1","pages":"1951"},"PeriodicalIF":2.9,"publicationDate":"2025-10-22","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145343868","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"CER1 as a manganese ion metabolism gene drives gastric cancer progression and therapeutic potential via oxidative stress and tumor microenvironment regulation.","authors":"Juan Hu, Ruian Zhu, Qiushi Huang, Xiaosong Li","doi":"10.1007/s12672-025-03502-2","DOIUrl":"https://doi.org/10.1007/s12672-025-03502-2","url":null,"abstract":"<p><strong>Background: </strong>Metal ions are vital for biological regulation and contribute to gastric cancer (GC) development, but the mechanisms are unclear. This study investigates the role of the manganese ion metabolism (MIM)-related gene CER1 in GC, focusing on how CER1 induces oxidative stress, contributes to tumor microenvironment heterogeneity, and its potential for targeted personalized therapy.</p><p><strong>Methods: </strong>Using single-cell RNA sequencing and multi-omics technologies, we characterized molecular subtypes of gastric cancer (GC) and explored the biological roles of the MIM family, elucidating genetic mechanisms of GC initiation and immune dysregulation.</p><p><strong>Results: </strong>Our analysis systematically clarified the pivotal role of the MIM gene family in GC, and revealed that CER1 promoted T cell exhaustion and facilitated immune evasion. The bioinformatics analysis indicated that CER1 may regulate tumor cell biological behavior through the NRF2/KEAP1-mediated oxidative stress signaling pathway. In summary, CER1, as a member of the MIM family, serves as a central hub in the oxidative stress and immune regulation.</p><p><strong>Conclusion: </strong>The in-depth investigation of CER1 within the MIM family has markedly deepened our understanding of the complex molecular mechanisms underlying GC. Through targeted manipulation of the NRF2/KEAP1 oxidative stress pathway and T cell function, CER1 emerges as a strategic pathway for potentially inhibiting tumor growth. This investigation outlines a strategic framework to facilitate the advancement of innovative treatment modalities.</p>","PeriodicalId":11148,"journal":{"name":"Discover. Oncology","volume":"16 1","pages":"1955"},"PeriodicalIF":2.9,"publicationDate":"2025-10-22","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145344197","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Molecular characterization of macrophage-related prognostic factors in glioblastoma revealed by combined analysis on single-cell and bulk transcriptome data.","authors":"Zhihao Wei, Hongchao Liu, Yajun Yang, Mengting Liu","doi":"10.1007/s12672-025-03816-1","DOIUrl":"https://doi.org/10.1007/s12672-025-03816-1","url":null,"abstract":"<p><strong>Background: </strong>Glioblastoma (GBM) is an aggressive primary tumor in the brain. The use of single-cell transcriptomic analysis can help to identify distinct cell subtypes and their functional states, and offer potential for advancing personalized therapeutic strategies for GBM.</p><p><strong>Methods: </strong>Single-cell data were preprocessed using the Seurat and Harmony packages, and differentially expressed genes (DEGs) were identified via the FindAllMarkers function. The high-dimensional WGCNA was carried out on the myeloid cells of single-cell data to screen out the macrophage-related modules, followed by performing enrichment analysis on the module genes with clusterProfiler package. Through univariate Cox-LASSO regression with package survival, the module genes were further screened and compressed to determine the core genes and construct a prognostic model. Patients were stratified by the cutoff values of the risk scores into high- and low-risk groups. The IOBR package was used to evaluate the differences in immune infiltration. The expression differences of immune checkpoints were compared, and the drug sensitivity of GBM patients was tested by the R package oncoPredict.</p><p><strong>Results: </strong>The proportion of Macro_PLIN2 subpopulation was significantly more in the tumor group, showing a higher activity in the blue and red modules. Eight core genes were further identified, namely SARNP, TGM2, G0S2, ACAP1, UPP1, POR, SLC43A3, and HPCAL1. Immune infiltration analysis revealed strong positive correlations between most core genes and the stromal score, immune score, and ESTIMATE score. The expression of PDCD1, PD-L1, CTLA4 and TIGIT in the high-risk group was significantly higher than those in the low-risk group. The drugs BI.2536, Daporinad, KU.55,933, and Ribociclib showed significant associations with the expression of the majority of core genes.</p><p><strong>Conclusion: </strong>This study reveals the molecular characteristics of key prognostic factors in GBM, highlighting the importance of immune cell abundance and drug sensitivity in glioma treatment, and provides potential biomarkers and therapeutic targets for future clinical research and treatment strategies.</p>","PeriodicalId":11148,"journal":{"name":"Discover. Oncology","volume":"16 1","pages":"1948"},"PeriodicalIF":2.9,"publicationDate":"2025-10-22","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145343879","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Causal roles of cathepsins family members in breast cancer subtypes: insights from Mendelian randomization and bioinformatics analysis.","authors":"Lin Tan, Junlian Xiang, Yi Lu, Xiaoli Zhong","doi":"10.1007/s12672-025-03787-3","DOIUrl":"https://doi.org/10.1007/s12672-025-03787-3","url":null,"abstract":"&lt;p&gt;&lt;strong&gt;Purpose: &lt;/strong&gt;This study aims to explore the causal association between members of the cathepsin family and breast cancer subtypes, with a focus on their expression profiles, prognostic significance, and potential molecular mechanisms in HER2-positive and HER2-negative breast cancer. Additionally, the study includes preliminary in vitro cell experiments to validate the functional relevance of key genes.&lt;/p&gt;&lt;p&gt;&lt;strong&gt;Methods: &lt;/strong&gt;This study employs the two-sample Mendelian randomization (MR) method to analyze the causal relationship between 10 members of the cathepsin family (CTSB, CTSE, CTSF, CTSG, CTSH, CTSL1, CTSL2, CTSO, CTSS, CTSZ) and breast cancer risk. Sensitivity analyses, including MR-Egger, Cochran's Q test, and MR-PRESSO, are used to validate the robustness of the results. Additionally, the study integrates differential gene expression analysis, prognostic impact analysis, single-cell analysis, protein-protein interaction (PPI) network construction, and targeted cell experiments (qRT-PCR for gene expression, CTSO overexpression model construction, CCK-8 proliferation assay, and wound healing migration assay) to systematically investigate the role of cathepsins in breast cancer.&lt;/p&gt;&lt;p&gt;&lt;strong&gt;Results: &lt;/strong&gt;MR analysis identified significant associations between CTSE and CTSO expression with breast cancer risk. Elevated CTSE expression was positively associated with both HER2-positive (OR = 1.108, P = 0.022) and HER2-negative (OR = 1.099, P = 0.009) breast cancer risk. In contrast, CTSO expression was inversely associated with HER2-negative breast cancer risk (OR = 0.913, P = 0.037). Differential expression analysis confirmed that CTSE was overexpressed in HER2-positive tumors, while CTSO was underexpressed across breast cancer subtypes. Prognostic analysis showed that high CTSE expression was linked to a favorable prognosis in HER2-positive breast cancer patients treated with chemotherapy, whereas high CTSO expression correlated with improved prognosis in HER2-negative patients. Single-cell analysis revealed that CTSO was highly expressed in immune cells and fibroblasts, while CTSE was mainly localized to cancerous epithelial cells. PPI and functional enrichment analyses suggested that CTSE is involved in lysosomal and protein digestion pathways, whereas CTSO is implicated in immune regulation and antigen processing. Cellular experiments revealed that qRT-PCR did not detect quantifiable levels of CTSE in breast cancer cell lines, while CTSO exhibited low expression across all breast cancer cell lines. After overexpressing CTSO in MDA-MB-231 cells, CCK-8 assays showed a significant reduction in cell proliferation, and wound healing assays demonstrated a marked inhibition of cell migration.&lt;/p&gt;&lt;p&gt;&lt;strong&gt;Conclusion: &lt;/strong&gt;This study provides multi-layered evidence for the association between members of the cathepsin family (particularly CTSE and CTSO) and breast cancer subtypes through MR analysis, bioinformati","PeriodicalId":11148,"journal":{"name":"Discover. Oncology","volume":"16 1","pages":"1949"},"PeriodicalIF":2.9,"publicationDate":"2025-10-22","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145344228","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Epidemiological trends in laryngeal cancer burden: insights from GBD 2021 and SEER databases.","authors":"Jie Zhang, Shuixiu Yu, Feng Wang, Weijuan Jiang, Lihua Fan","doi":"10.1007/s12672-025-03725-3","DOIUrl":"https://doi.org/10.1007/s12672-025-03725-3","url":null,"abstract":"<p><strong>Background: </strong>The burden of laryngeal cancer (LC) warrants further exploration to better understand its current status and trends.</p><p><strong>Methods: </strong>Using data from the Global Burden of Disease (GBD) 2021, we assessed age-standardized incidence, mortality, and disability-adjusted life years (DALYs) rates for LC at the global, regional, and national levels. The LC burden was decomposed based on population size, age structure, and epidemiological changes, and cross-country inequalities were quantified using the World Health Organization's recommended standard health equity approach. Additionally, data from the Surveillance, Epidemiology, and End Results (SEER) database were combined with joinpoint regression analysis to determine the average annual percentage change (AAPC) in LC incidence and mortality trends in the United States.</p><p><strong>Results: </strong>GBD data showed a global decline in LC incidence and mortality rates from 1990 to 2021, with notable gender disparities and a higher burden in males. Key risk factors included smoking, alcohol use, asbestos, and sulfur exposure. Decomposition analysis identified population growth as the main driver of the LC burden, with regional and gender differences in aging and epidemiological trends. Inequality analysis revealed higher DALYs in low-SDI countries, with a widening gap over time. SEER data indicated a declining LC incidence in the US (1992-2021), and incidence-based mortality(IBM) increased until 2003 before declining.</p><p><strong>Conclusions: </strong>From 1990 to 2021, global LC incidence and mortality declined, with a higher burden in males. The gap in LC burden between high and low SDI countries has increased. These findings highlight the need for targeted public health strategies to address both epidemiological trends and socio-demographic inequalities.</p>","PeriodicalId":11148,"journal":{"name":"Discover. Oncology","volume":"16 1","pages":"1946"},"PeriodicalIF":2.9,"publicationDate":"2025-10-22","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145344233","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Amino acid metabolism-related LncRNAs as prognostic biomarkers and predictors of immunotherapy response in hepatocellular carcinoma.","authors":"Jiaxing Zhang, Xiaojing Zhu, Long Hu, Liyue Yu, Yan Xu","doi":"10.1007/s12672-025-03789-1","DOIUrl":"https://doi.org/10.1007/s12672-025-03789-1","url":null,"abstract":"<p><strong>Background: </strong>HCC has a high mortality rate among common malignancies. Finding the pathway that is involved with HCC is the main challenge in targeting metabolism for cancer therapy.</p><p><strong>Methods: </strong>Based on transcription data from the TCGA database, Univariate Cox analysis, LASSO, and Multivariate Cox analysis were used to identify hub AAM-related lncRNAs and construct a risk model. Then K-M survival analysis, time-dependent ROC curve analysis, genetic alterations, functional enrichment, immune infiltration status, and immunotherapy response were conducted. Finally, the effect of the characteristic gene AL590681.1 across different HCC cell lines was assessed.</p><p><strong>Results: </strong>24 lncRNAs were involved in AAM and prognostic factors, and 4 lncRNAs were in our risk model. Patients in the high-risk group had a lower OS rate than patients in the low-risk group. The high-risk group had more immunosuppressive immune cells infiltrating and expressing CD276, CTLA4 and TIGIT. Patients in the high-risk group could had better survival prospects with an anti-PD1 treatment. Finally, the key gene AL590681.1 was overexpressed in various HCC cell lines and could enhance HCC cell activity.</p><p><strong>Conclusion: </strong>We developed a novel risk model for HCC patients with AAM-related lncRNAs, which could help predict the prognosis and response to immunotherapy.</p>","PeriodicalId":11148,"journal":{"name":"Discover. Oncology","volume":"16 1","pages":"1947"},"PeriodicalIF":2.9,"publicationDate":"2025-10-22","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145344237","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}